Anti-Aging Hormone Could Make You Smarter

Klotho (right) is one of the three Greek Fates depicted in this Flemish tapestry at the Victoria and Albert Museum in London.

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Originally published on May 8, 2014 7:49 pm

A hormone associated with longevity also appears to make people's brains work better.

The finding in Cell Reports could someday lead to drugs that improve memory and learning, researchers say.

"We've discovered a way to potentially boost cognition," says Dena Dubal, one of the study's authors who does research on aging and the brain at the University of California, San Francisco. And that could mean "a very new way to treat diseases," ranging from Alzheimer's to schizophrenia, she says.

The hormone is named Klotho, after the Fate from Greek mythology who spins the thread of life. Scientists have known for more than a decade that people and animals tend to live longer if they have high levels of Klotho in their bodies.

And that led Dubal and researchers at the Gladstone Institutes to wonder whether a hormone that protects the body against aging might also protect the brain. So the team set out to see whether Klotho offered a way to "prevent the cognitive decline that comes with aging," Dubal says.

To find out, they studied more than 700 people between the ages of 52 and 85. About 1 in 5 of these people had a form of the Klotho gene that causes their bodies to produce high levels of the Klotho hormone.

The team expected to find that people with high levels of the hormone experienced less cognitive decline than people with lower levels. "In fact what we found was not consistent with our hypothesis," Dubal says. "We were completely surprised."

What they found was that the people with lots of Klotho experienced just as much cognitive decline as other people. Their brains weren't protected against aging at all. But their brains were different nonetheless, Dubal says.

"Those that carried the genetic variant that increased their Klotho levels showed better cognitive performance across the lifespan," Dubal says. At any given age, people with lots of Klotho scored higher on tests of learning and memory, language and attention, she says.

So instead of discovering a way to protect the brain from aging, the team had found a hormone that appears to make people smarter.

To learn more, the team began studying mice that had been genetically engineered to produce high levels of the mouse version of Klotho. And this time, the researchers got exactly the result they hoped for. "Elevating klotho made the mice smarter across all the cognitive tests that we put them through," Dubal says

A look at the brains of these mice suggested a reason. There was evidence that in areas involved in learning and memory, Klotho was causing a change that strengthened the connections between brain cells.

All this suggests that a drug able to raise levels of Klotho might be able to help people with Alzheimer's and other brain diseases, Dubal says, even if the drug didn't stop the disease itself. "Our goal and vision is that there will be a therapy that improves the lives of people that are suffering from diseases of the brain," Dubal says.

But any treatment based on manipulating Klotho levels in people remains years away, says Molly Wagster, who oversees research on cognitive change at the National Institute on Aging. The NIA and National Institute of Neurological Disorders and Stroke both helped fund the research.

"The beauty of this study is that the finding gives us another place to look, another path to take as we try to determine targets for the development of drugs," Wagster says. It also raises questions about whether Klotho levels may be influenced by diet, exercise or brain activity – all of which have been shown to affect cognitive function in older people, she says.

There's a lot researchers still don't know about the Klotho, which was discovered in 1997. For example, it's not clear why carrying one copy of the gene associated with higher levels of the hormone improves cognitive function while carrying two copies seems to impair function.

But knowing that a naturally occurring hormone affects cognition in both mice and people should speed efforts to find treatments for diseases that cause impaired brain function, Wagster says.

Copyright 2014 NPR. To see more, visit http://www.npr.org/.

Transcript

MELISSA BLOCK, HOST:

This is ALL THINGS CONSIDERED from NPR News. I'm Melissa Block.

ROBERT SIEGEL, HOST:

And I'm Robert Siegel.

Scientists say a hormone associated with longevity also appears to make people smarter. NPR's Jon Hamilton reports that the finding out today could someday lead to drugs that improve memory and learning.

JON HAMILTON, BYLINE: The hormone is called klotho, after the fate from Greek mythology who spins the thread of life. Scientists have known for more than a decade that people and animals tend to live longer if they have high levels of klotho in their bodies. And that led a team of researchers to wonder whether a hormone that protects the body against aging might also protect the brain.

Dena Dubal at the University of California, San Francisco, says their original goal was to answer a really intriguing question.

DENA DUBAL: Can we actually block or slow the aging process and prevent the cognitive decline that comes with aging?

HAMILTON: To find out, they studied hundreds of people who carry a form of the klotho gene that causes their bodies to produce high levels of the klotho hormone.

Dubal says what the team expected to find was that these people would experience less cognitive decline in their 60s and 70s and 80s than people with lower levels of klotho.

DUBAL: In fact, what we found was not consistent with our hypothesis. We were completely surprised by our findings.

HAMILTON: What they found was that the people with lots of klotho experienced just as much cognitive decline as other people. Their brains were not protected against aging. But Dubal says the results also showed that there was something different about their brains.

DUBAL: Those that carried that genetic variant that increased their klotho levels, they showed better cognitive performance across the lifespan.

HAMILTON: At any given age, people with lots of klotho scored higher on tests of learning and memory, language, attention, and spatial ability. So instead of discovering a way to protect the brain from aging, the team had found a hormone that appears to make people smarter.

To learn more, Dubal says, the team began studying mice that were genetically engineered to produce high levels of the mouse version of klotho. And this time, they weren't surprised by what they found.

DUBAL: Elevating klotho made the mice smarter across all the cognitive tests that we put them through.

HAMILTON: Tests like remembering how to get through a maze. And a look at the brains of these mice, suggested a reason. There was evidence that in areas involved in learning and memory, klotho was strengthening the connections between brain cells.

Dubal says all this suggests that a drug able to raise levels of klotho might be able to help people with Alzheimer's and other brain diseases, even if it doesn't stop the disease itself.

DUBAL: Our goal and vision is that there will be a therapy. We hope for a therapy that improves the lives of people that are suffering from diseases of the brain.

HAMILTON: But that's far from certain. Molly Wagster is from the National Institutes of Health, which helped fund the klotho research.

MOLLY WAGSTER: The beauty of this study is that the finding gives us another place to look, another path to take as we try to determine targets for development of drugs.

HAMILTON: Wagster says it also raises questions about whether klotho levels are affected by some of the things already known to be good for aging brains.

WAGSTER: Even diet or exercise or cognitive engagement, these things may stimulate klotho.

HAMILTON: But Wagster says there's a lot researchers still don't know about the hormone and how it interacts with other factors involved in both brain function and aging.

WAGSTER: The more pieces of the puzzle we have, the clearer the picture becomes as we're putting it together. And I find this to be another piece of that puzzle.